Tegaserod, a 5-HT4 receptor partial agonist, decreases sensitivity to rectal distension in healthy subjects.

BACKGROUND: Tegaserod reduces the symptoms associated with irritable bowel syndrome, and anti-nociceptive effects have been demonstrated in animals. Its effect on the rectal sensitivity in humans has not been delineated clearly. AIM: To evaluate the action of tegaserod on rectal sensitivity in response to distension by means of a reflexological technique based on electrophysiological recordings of the RIII nociceptive reflex. METHODS: A randomized, double-blind, placebo-controlled study, performed in 20 healthy women, quantified the effects of slow or rapid rectal distensions on the RIII reflex at baseline and on day 8 following treatment with either placebo or tegaserod (6 mg b.d.). RESULTS: At baseline, slow distensions performed up to the pain threshold induced gradual inhibitions of the RIII reflex. On day 8, these inhibitory effects were significantly reduced in the tegaserod group, but not in the placebo group (P = 0.0001). The effects of rapid distensions were not significantly modified by tegaserod or placebo. The intensity of subjective pain perception and rectal compliance were not altered by either treatment. CONCLUSION: These results suggest that tegaserod reduces the sensitivity to rectal distension in healthy subjects and interacts with the processing of sensory visceral information.

Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death.

BACKGROUND: In patients with hepatitis C virus (HCV) infection and cirrhosis, long term outcome and the incidence of hepatocellular carcinoma (HCC) are still debated. DESIGN: From January 1987 to January 1997, 416 patients (240 male, median age 57 years) with uncomplicated Child-Pugh A HCV related cirrhosis were followed in two Paris area centres from diagnosis of cirrhosis until death or reference date (1 June 1998). The analysis used a three state disability model generalising the Cox model. RESULTS: Of the 416 patients, 60 developed HCC with a five year rate of 13.4% (95% confidence interval (CI) 9.0-17.8%) and 83 died (including 34 with HCC), with a five year death rate of 15.3% (95% CI 12.6-18.0%). By multivariable analysis, time to HCC relied on age (hazard ratio (HR) 1.05 per year; p=0.0005), male sex (HR 2.13; p=0.01), oesophageal varices (HR 2.36; p= 0.008), decreased platelet count (HR 0.99; p=0. 03), and bilirubin level (HR 1.01; p=0.003), while death after HCC was mainly related to tobacco consumption (HR 1.04; p=0.0006). In contrast, death free of HCC was dependent on age (HR 1.04; p=0.01), oesophageal varices (HR 2.75; p=0.001), low platelet count (HR 0.99; p=0.006), and albumin level (HR 0.90; p=0.0001). CONCLUSION: The incidence of HCC and mortality should be higher in these patients than previously stated, and prognostic factors of HCC and death are closely related age and symptoms of portal hypertension.